The energy requirements of contracting muscles involved in high-intensity exercise may increase 100-fold relative to resting muscles, thereby exceeding the aerobic energy production capacity of the cells (Westerblad H, et al. News Physiol Sci. 2002 February; 17:17-21). In this case, anaerobic metabolism is required to provide additional energy. However, high-intensity exercise results in an eventual reduced capacity for muscular contractile function, or commonly known as fatigue. Thus, there is seemingly a link between anaerobic metabolism and fatigue.
In a 2000 review on the role of creatine in skeletal muscle, Casey and Greenhaff provide a thorough overview of energy supply and its utilization in muscle (Casey A, et al. Am J Clin Nutr. 2000 August; 72(2 Suppl):607S-17S). ATP is the direct energy source for contracting muscle as the energy needed for muscular contraction is released by the dephosphorylation of ATP to yield the low-energy metabolite Adenosine Diphosphate, hereinafter referred to as ADP and inorganic phosphate (Pi) according to the following reaction:ATP+H2O→ADP+Pi+H++energy  (reaction 1)Therefore, it is naturally observed that the function of muscle is largely dependent upon the availability of ATP. However, the concentration of ATP available in muscle at rest prior to the start of exercise, is only sufficient to supply about 1-2 seconds of the energy required for intense activity. ATP, however, can be readily and rapidly regenerated through the anaerobic dephosphorylation of available phosphocreatine. However, like that of ATP, the concentration of phosphocreatine in muscle is low and only sufficient to sustain muscular activity for an additional 6 seconds. After repeated bouts of contraction, muscle phosphocreatine levels become nearly depleted (Greenhaff P L, et al. J. Physiol. 1993 January; 460:443-53). Naturally, fatigue, although likely multifaceted in terms of biochemical events, is the point at which the energy required by contracting muscle exceeds the level available either from the stored supply of ATP or the indirect synthesis of high-energy ATP through phosphocreatine dephosphorylation.
CK is an ATP-dependent enzyme, which, using magnesium, hereinafter referred to as Mg2+, as a co-factor, phosphoylates ADP to ATP. CK is normally found within cells however, when muscle cells are damaged the cells often rupture and the normally cell-bound proteins leak out in to the surrounding serum. Since the phosphoylation reaction is ATP-dependent, an elevated presence of CK outside the cells ultimately leads to the consumption of the high-energy molecule ATP. The consumption of ATP by CK in the serum is detrimental to cells, which requires ATP as an energy source for energetic properties in relation to muscular contractions.